Browsing by Author "Zhang, Hao"

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Honeysuckle aqueous extract and induced let-7a suppress dengue virus type 2 replication and pathogenesis
(2017-02-23)
Lee, Ying-Ray
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Yeh, Siao-Fen
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Ruan, Xiao-Ming
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Zhang, Hao
;
Hsu, Sheng-Da
Ethnopharmacological relevance: Honeysuckle (Lonicera japonica Thunb.), a traditional Chinese herb, has widely been used to treat pathogen infection. However, the underlying-mechanism remains elusive. Aims of the study: To reveal the host microRNA (miRNA) profile with the anti-viral activity after honeysuckle treatment. Materials and methods: Here we reveal the differentially expressed miRNAs by Solexa (R) deep sequencing from the blood of human and mice after the aqueous extract treatment. Among these overexpressed innate miRNAs both in human and mice, let-7a is able to target the NS1 region (nt 3313-3330) of dengue virus (DENV) serotypes 1, 2 and 4 predicated by the target predication software. Results: We confirmed that let-7a could target DENV2 at the predicated NS1 sequence and suppress DENV2 replication demonstrated by luciferase-reporter activity, RT-PCR, real-time PCR, Western blotting and plaque assay. ICR-suckling mice consumed honeysuckle aqueous extract either before or after intracranial injection with DENV2 showed decreased levels of NS1 RNA and protein expression accompanied with alleviated disease symptoms, decreased virus load, and prolonged survival time. Similar results were observed when DENV2infected mice were intracranially injected with let-7a. Conclusion: We reveal that honeysuckle attenuates DENY replication and related pathogenesis in vivo through induction of let-7a expression. This study opens a new direction for prevention and treatment of DENY infection through induction of the innate miRNA let-7a by honeysuckle.
Theoretical Studies on Catalysis Mechanisms of Serum Paraoxonase 1 and Phosphotriesterase Diisopropyl Fluorophosphatase Suggest the Alteration of Substrate Preference from Paraoxonase to DFP
(2018-07-01)
Zhang, Hao
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Yang, Ling
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Ma, Ying-Ying
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Zhu, Chaoyuan
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Lin, Shenghsien
The calcium-dependent beta-propeller proteins mammalian serum paraoxonase 1 (PON1) and phosphotriesterase diisopropyl fluorophosphatase (DFPase) catalyze the hydrolysis of organophosphorus compounds and enhance hydrolysis of various nerve agents. In the present work, the phosphotriesterase activity development between PON1 and DFPase was investigated by using the hybrid density functional theory method B3LYP. Based on the active-site difference between PON1 and DFPase, both the wild type and the mutant (a water molecule replacing Asn270 in PON1) models were designed. The results indicated that the substitution of a water molecule for Asn270 in PON1 had little effect on the enzyme activity in kinetics, while being more efficient in thermodynamics, which is essential for DFP hydrolysis. Structure comparisons of evolutionarily related enzymes show that the mutation of Asn270 leads to the catalytic Ca2+ ion indirectly connecting the buried structural Ca2+ ion via hydrogen bonds in DFPase. It can reduce the plasticity of enzymatic structure, and possibly change the substrate preference from paraoxon to DFP, which implies an evolutionary transition from mono- to dinuclear catalytic centers. Our studies shed light on the investigation of enzyme catalysis mechanism from an evolutionary perspective.